After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-18F-fluoroestradiol (18F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of 18F-4FMFES with that of 16α-18F-fluoroestradiol (18F-FES) in ER-positive (ER+) breast cancer patients. Methods: Patients diagnosed with ER+ breast cancer (n = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, 18F-FES and 18F-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUVmean of nonspecific tissues and the SUVmax of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. Results: Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability of 18F-4FMFES over 18F-FES. Although for most foci 18F-4FMFES PET had an SUVmax similar to that of 18F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues for 18F-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with 18F-FES. Consequently, image quality was considerably improved using 18F-4FMFES, with lower overall background activity. As a result, 18F-4FMFES successfully identified 9 more lesions than 18F-FES. Conclusion: This phase II study with ER+ breast cancer patients showed that 18F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than 18F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.

中文翻译：

---

使用新型放射性示踪剂18F-4FMFES通过PET在雌激素受体阳性乳腺癌患者中改善的雌激素受体评估：正在进行的II期临床试验。

在令人鼓舞的新型雌激素受体（ER）PET放射性示踪剂4-氟-11β-甲氧基-16α-18F-氟雌二醇（18F-4FMFES）的临床前和人体剂量测定结果之后，开始了一项II期临床试验，以比较PET成像的诊断潜力ER阳性（ER +）乳腺癌患者中18F-4FMFES和16α-18F-氟雌二醇（18F-FES）的差异。方法：本研究招募了被诊断为ER +乳腺癌的患者（n = 31），其中包括6例行了乳房切除术或腋窝淋巴结清扫术的患者。对于每位患者，依次（一周内）以随机顺序进行18F-FES和18F-4FMFES PET / CT扫描。注射任何一种放射性示踪剂后一小时，均获得了从头到大腿的静态扫描，每个床位采集2分钟。注射后在不同时间采集血样，通过反相薄层色谱法评估每种示踪剂的新陈代谢。对于每个检测到的病变，评估非特异性组织的SUVmean和肿瘤的SUVmax，并计算肿瘤与非特异性器官的比率。结果：注射示踪剂后60分钟的血液代谢产物分析显示18F-4FMFES的代谢稳定性比18F-FES增加了2.5倍。尽管对于大多数病灶，18F-4FMFES PET的SUVmax与18F-FES PET的相似，但在所有情况下，肿瘤的对比度都得到了显着改善。在18F-4FMFES的非特异性组织中始终观察到较低的摄取，与18F-FES相比，血池活性明显降低了4倍。因此，使用18F-4FMFES可以显着提高图像质量，而总体背景活动较低。因此，与18F-FES相比，18F-4FMFES成功地鉴定出9个以上的病变。结论：这项针对ER +乳腺癌患者的II期研究表明，与18F-FES PET相比，18F-4FMFES PET可实现更低的非特异性信号和更好的肿瘤造影剂，从而提高诊断信心并降低假阴性诊断率。